The proposed Collaborative Corneal Transplantation Studies (CCTS) consist of two multicenter studies of the effectiveness of histocompatibility matching in preventing corneal allograft rejection in high risk eyes. Eyes with corneal stromal vascularization or a history of corneal graft rejection will be eligible for the CCTS. The Crossmatch Study will test the effectiveness of negative donor-recipient crossmatching in preventing corneal graft rejection in high risk patients who have detectable lymphocytotoxic antibodies. Eyes will be randomized to receive either a positively crossmatched donor cornea or a negatively crossmatched donor cornea. The HLA Matching Study will assess the effectiveness of varying degrees of HLA-A, B donor-recipient matching and of HLA-DR donor-recipient matching in preventing corneal graft rejection in high risk patients without detectable lymphocytotoxic antibodies. Patients will be assigned corneas with different degrees of HLA matching. In both studies, treatment assignment and patient followup will be performed in a double masked fashion. Patients will be followed closely during the first postoperative year with continued followup for two additional years. Patients will follow a standard topical steroid medication plan after surgery. The two studies will be carried out by a single study organization. The leading corneal transplant centers will work in collaboration with their local tissue typing laboratory and cornea procuring eye bank in recruiting approximately 800 patients and 2500 corneas for the CCTS over a three year period. A Central HLA Laboratory will oversee standardization among the laboratories. A Coordinating Center will serve as the central data collection, data analysis, and administrative center.